Bio-Inspired Zwitterionic Self-Assembling Molecule for Modification of Targeting Hyperthermia Agent(1/3)

Surface self-assembling modifier for nanomaterials provides facile and effective approach to fine tune physicochemical interfacial properties, keep good colloidal stability, enable bio-functionalization and possess environmental responsiveness. However, conventional modifiers based on poly(ethylene glycol) (PEG) are susceptible to high temperature and ionic strength, leading to loss of hydration, non-specific adsorption and colloidal aggregation. These problems hamper wide applications of nanomaterials. In this proposal, we will develop a novel bioinspired zwitterionic cysteine betaine (Cys-b) as a surface modifier. Cys-b will be applied to hollow Ag@Au nanoshells as functional hyperthermia agent for targeted delivery to HER2-positive MDA-MB-453 breast cancer cells for hyperthermia treatment. The agent comprises of with strong absorption in a NIR range and bioinspired zwitterionic cysteine betaine (Cys-b) ligand. The hypothesis bases on the fact that the hydration mechanism of PEG-based relies on hydrogen bonding that is unstable at a high temperature, while that of zwitterionic materials on ionic solvation that is insensible to heat. In other words, the Cys-b adsorbates can afford effective antifouling properties, chemical and colloidal stability under the hyperthermia conditions. Therefore, we will prove the targeted therapeutic effect of the anti-HER2 antibody-conjugated Cys-b nanoshells for breast cancer cells. The research will be realized by three directions: 1.synthesis and physicochemical characterization of Cys-b and nanoshells; 2. Development of hyperthermia agent based on Cys-b nanoshells for breast cancer cells; 3. Fundamental investigation and applications of responsive 2D hierarchical Cys-b assemblies; 4. Development of substrate-independent antifouling coatings based on polydopamine. The aim of the study is to establish a novel zwitterionic surface ligand for targeting hyperthermia agent by integrating plasmonic nanomaterials and cutting-edge surface chemistry. The proposed work spams from material design, fundamental physicochemical investigation to biomedical applications. In addition, we will establish the theory of ionic self-assembly as a guiding principal for responsive intelligent biointerfaces. Such an approach sets the stage for advancement in biocompatibility, intelligence and versatility of medical devices. Though materials development, characterization and implementation, we will promote the fields of biomaterials science and technology, promote the core capability of biomedical industries and educate high-level researchers.